Publicaciones científicas

Cilta-cel or Standard Care in Lenalidomide-Refractory Multiple Myeloma

27-jul-2023 | Revista: New England Journal of Medicine

Jesús San-Miguel  1 , Binod Dhakal  1 , Kwee Yong  1 , Andrew Spencer  1 , Sébastien Anguille  1 , María-Victoria Mateos  1 , Carlos Fernández de Larrea  1 , Joaquín Martínez-López  1 , Philippe Moreau  1 , Cyrille Touzeau  1 , Xavier Leleu  1 , Irit Avivi  1 , Michele Cavo  1 , Tadao Ishida  1 , Seok Jin Kim  1 , Wilfried Roeloffzen  1 , Niels W C J van de Donk  1 , Dominik Dytfeld  1 , Surbhi Sidana  1 , Luciano J Costa  1 , Albert Oriol  1 , Rakesh Popat  1 , Abdullah M Khan  1 , Yaël C Cohen  1 , P Joy Ho  1 , James Griffin  1 , Nikoletta Lendvai  1 , Carolina Lonardi  1 , Ana Slaughter  1 , Jordan M Schecter  1 , Carolyn C Jackson  1 , Kaitlyn Connors  1 , Katherine Li  1 , Enrique Zudaire  1 , Diana Chen  1 , Jane Gilbert  1 , Tzu-Min Yeh  1 , Sarah Nagle  1 , Erika Florendo  1 , Lida Pacaud  1 , Nitin Patel  1 , Simon J Harrison  1 , Hermann Einsele  1


Background: Ciltacabtagene autoleucel (cilta-cel), a B-cell maturation antigen (BCMA)-directed CAR T-cell therapy, is effective in heavily pretreated patients with relapsed or refractory multiple myeloma. We investigated cilta-cel in earlier treatment lines in patients with lenalidomide-refractory disease.

Methods: In this phase 3, randomized, open-label trial, we assigned patients with lenalidomide-refractory multiple myeloma to receive cilta-cel or the physician's choice of effective standard care. All the patients had received one to three previous lines of treatment. The primary outcome was progression-free survival.

Results: A total of 419 patients underwent randomization (208 to receive cilta-cel and 211 to receive standard care). At a median follow-up of 15.9 months (range, 0.1 to 27.3), the median progression-free survival was not reached in the cilta-cel group and was 11.8 months in the standard-care group (hazard ratio, 0.26; 95% confidence interval [CI], 0.18 to 0.38; P<0.001). Progression-free survival at 12 months was 75.9% (95% CI, 69.4 to 81.1) in the cilta-cel group and 48.6% (95% CI, 41.5 to 55.3) in the standard-care group. More patients in the cilta-cel group than in the standard-care group had an overall response (84.6% vs. 67.3%), a complete response or better (73.1% vs. 21.8%), and an absence of minimal residual disease (60.6% vs. 15.6%). Death from any cause was reported in 39 patients and 46 patients, respectively (hazard ratio, 0.78; 95% CI, 0.5 to 1.2). Most patients reported grade 3 or 4 adverse events during treatment. Among the 176 patients who received cilta-cel in the as-treated population, 134 (76.1%) had cytokine release syndrome (grade 3 or 4, 1.1%; no grade 5), 8 (4.5%) had immune effector cell-associated neurotoxicity syndrome (all grade 1 or 2), 1 had movement and neurocognitive symptoms (grade 1), 16 (9.1%) had cranial nerve palsy (grade 2, 8.0%; grade 3, 1.1%), and 5 (2.8%) had CAR-T-related peripheral neuropathy (grade 1 or 2, 2.3%; grade 3, 0.6%).

Conclusions: A single cilta-cel infusion resulted in a lower risk of disease progression or death than standard care in lenalidomide-refractory patients with multiple myeloma who had received one to three previous therapies. (Funded by Janssen and Legend Biotech; CARTITUDE-4 ClinicalTrials.gov number, NCT04181827.).

CITA DEL ARTÍCULO  N Engl J Med. 2023 Jul 27;389(4):335-347.  doi: 10.1056/NEJMoa2303379. Epub 2023 Jun 5